Study Demonstrates Essential Role of ZEAXANTHIN in Eye Health Source of Article
Schepens/Harvard study provides direct proof of dietary nutrient's essential
role in protecting the retina from the damaging effects of light. Research performed
at Schepens Eye Research Institute and Department of Ophthalmology, Harvard
Medical School has established that the dietary zeaxanthin (zee-uh-zan'-thin)
plays an essential role in protecting the retina of the eye from the damaging
effects of light.
From the many carotenoids in the diet, the human retina selectively accumulates
only two: zeaxanthin and lutein. Their concentration is so high in the macula,
(the retinal region responsible for fine visual activities) that the carotenoids
are visible as a dark yellow spot called the macular pigment. Because
these carotenoids absorb blue light, and because they are powerful antioxidants,
scientists have hypothesized that they protect the retina. Working with quail
as an animal model, the Schepens project provided the first direct experimental
evidence that carotenoids do protect the retina.
Clinical Relevance of the New Findings Macular pigment has been implicated as
a risk factor in age-related macular degeneration (AMD), the most prevalent
cause of vision loss in the elderly. Vision loss in AMD is due to the irreversible
death of photoreceptors and/or the invasion of leaky, unwanted blood vessels
into the retina. At advanced stages of this progressive disease, everyday activities
such as reading, driving, or even seeing the face of a loved one become impossible.
It is estimated that more than 17 million Americans may have symptoms of AMD
and that 2 million having functional blindness; 500,000 new cases are diagnosed
each year. Some clinical studies have found evidence that people
with higher dietary or serum levels of zeaxanthin and lutein had reduced risk
for advanced stages of age-related macular degeneration, but others have found
no association.
Significantly lower macular pigment levels have been found in people with factors
known to increase risk for AMD (e.g. smoking), in eyes with AMD, and in eyes
at high risk for AMD. Epidemiologic studies have shown that people with higher
dietary or plasma lutein/zeaxanthin have reduced risk for advanced stages of
AMD. It is not yet clear whether the reduced risk for AMD is due to lutein/zeaxanthin
or due to some other nutrient in the plants containing carotenoids. The Schepens
work has clearly shown that the carotenoids protect the retina from light damage
in animals. Some studies, but not all, have identified light damage as a risk
factor in AMD.
To test this hypothesized protection, the team selected Japanese quail because
the retina resembles the human macula in having more cone photoreceptor s than
rods and in highly selective accumulation of zeaxanthin and lutein from their
diet. Rodents were not studied because their retinas have very few cones and
do not accumulate carotenoids. The studies examined the effect of manipulating
dietary carotenoids on light damage to retinas. C. Kathleen Dorey, principal
investigator formerly with Schepens and now with R&D Consulting, and her
colleagues raised quail on diets that were normal, carotenoid-deficient, or
carotenoid-deficient supplemented with high doses of zeaxanthin.
In the short-term study, reported in the November 2002 issue of Investigative
Ophthalmology and Visual Science (IOVS), the team divided the carotenoid-deficient
quail into two groups, and for one week preceding light damage, they fed one
group zeaxanthin-supplemented diet. The study established that photoprotection
was strongly correlated with the concentration of zeaxanthin in the retinas
of the quail. Retinas with low concentrations of zeaxanthin had suffered severe
light damage, as evidenced by a very high number of apoptotic photoreceptor
cells, while the group with high zeaxanthin concentrations had minimal damage.
Apoptosis is programmed cell death, the final common pathway for photoreceptor
death in retinal degeneration.
In the long-term study, reported in the November 2002 issue of Experimental
Eye Research, groups of quail were raised for six months on carotenoid-deficient,
normal or zeaxanthin-supplemented diets before exposure to brighter light.
The results showed extensive damage to the retina in the carotenoid-deficient
animals, as evidenced by large numbers of both dying photoreceptors and gaps
or "ghosts" marking sites where photoreceptors had died. The group of
quail with normal dietary levels of zeaxanthin showed significantly less retinal
damage than did the zeaxanthin-deprived group, while the quail group receiving
high levels of zeaxanthin had few ghosts in their retinas.
These experiments by Dr. Dorey's team showed protection of both rod and cone
photoreceptors. The research further demonstrated that retinas were protected
by both zeaxanthin and another antioxidant, vitamin E. Damage in these
experiments was clearly reduced by zeaxanthin and tocopherol, but not lutein.
Further experiments would be needed to determine whether elevated lutein would
offer protection.
These results are reminiscent of the early 20th century discovery of the role
of vitamins. In those experiments, extensive efforts were made to show
that dietary deficiency of a compound caused health problems that were reversed
by adding the substance back to the animal's diet.
The results of the Schepens studies come on the heels of the Age Related Eye
Disease Study (AREDS), sponsored by the National Eye Institute of the National
Institutes of Health, which concluded that daily consumption of a formula containing
high doses of dietary antioxidants are effective in slowing the progression
of AMD in patients with advanced stages of the disease. It is noteworthy that
zeaxanthin and lutein, two antioxidants selectively concentrated by the macula,
were not commercially available when the AREDS began and were, therefore, not
able to be included in that study.
The Implications for Macular Degeneration Commenting on the implications of
the Schepens studies, Dr. Dorey said: "AMD is a multi-factorial disease clearly
influenced by both genetic (family history) and environmental factors (diet,
and possibly light history). The retina is constantly exposed to oxidative
injury, a leading candidate for initiating or accelerating retinal degeneration.
Zeaxanthin is well suited to its role in maintaining retinal health, and may
be an important strategy to prevent or intervene in macular degeneration. It
accumulates in the macula where it absorbs harmful blue wavelength light, and
it accumulates in the RPE and the most vulnerable portions of the photoreceptors
where its potent anti-oxidant capacity can prevent oxidative damage, a problem
that increases with aging.
"Our studies showed that light damage was strongly influenced by the amount
of zeaxanthin in the retina, and that significantly greater retinal protection
was provided at dietary levels higher than those normally occurring in the diet.
Zeaxanthin has been extensively studied for safety and has been reviewed as
a dietary ingredient by the FDA. We hope this work further stimulates interest
in clinical trials, and believe that zeaxanthin has a potential to eventually
complement other strategies to improve the treatment of this vision-robbing
disease."
# # #
The research team included: ** Lauren R. Thomson, M.D. Yoko Toyoda, M.D. Z-Y
Wong, M.D., Francois C. Delori, Ph.D., and C. Kathleen Dorey, Ph.D. (now with
R&D Consulting) at Schepens Eye Research Institute. ** Kevin M. Garnett,
BS, MBA at Applied Food Biotechnology, Inc. (O'Fallon, Mo.) ** Kimberly M. Cheng,
Ph.D. and Cathleen R. Nichols at Department of Animal Sciences, University of
British Columbia (Vancouver) ** Neal E. Craft, Craft Technologies, Inc. (Wilson,
N.C.)
Expert Commentary on Research Findings
"The two articles from Dr. Dorey's group use quail as a model because these
birds concentrate the "macular pigments" (the carotenoids, lutein and zeaxanthin)
in their retinas, although in a manner different from humans. Some (but not
all) epidemiologic studies on nutrition and eye diseases have shown that these
yellow compounds may help protect our eyes from developing age-related macular
degeneration (AMD), a common and devastatin g disease of the retina. The researchers
fed some of their birds a diet rich in zeaxanthin for six months, and then observed
the effect of very bright light on the Z-fed and on the control quail. Light
of this intensity and duration caused much more damage to the retinas of the
control animals than to those of the Z-fed birds, who had accumulated lots of
Z in their retinas.
"The importance of these results is that they are the first direct, experimental
evidence that Z can protect the retina, preventing photoreceptor cells (the
rods and cones) from dying from an insult (in this case, bright light). The
thinking is that Z may also protect the retina from whatever insults, at present
unknown, result in AMD. It is also important that dietary supplement ation with
Z resulted in higher concentrations of this compound in the quail retina. Zeaxanthin
is found in some yellow, orange, and red fruits and vegetables; corn is a good
source for people. However, it would be easier to raise the level of Z in the
retina through supplementation, in those people who have low levels of macular
pigment. (This level can be measured by a simple, non-invasive test.) Although
lutein-containing supplements have been on the market for some time, this is
not yet true for zeaxanthin." Alice Adler, Ph.D. Schepens Eye Research Institute.
"We first reported the beneficial effect of dietary zeaxanthin/lutein in reducing
the risk of age-related macular degeneration in JAMA, 1994. Dr. Dorey should
be congratulated for her innovative research, which applied and expanded these
clinical research findings to an experimental animal model. Her research supports
our findings and adds to the growing knowledge that the macular pigments play
an important role in ocular health. The recently completed randomized trial
component of the Age-Related Eye Disease Study demonstrated that supplementation
with antioxidant vitamins C, E and beta-carotene, as well the mineral zinc,
reduces the rate of AMD progressio n by 25 percent over five years. The growing
evidence that the carotenoids -- zeaxanthin and lutein -- have beneficial effects
requires more emphasis and a possible randomized trial to test their role in
the prevention of the serious visual consequences associated with the growing
burden of macular degeneration among the elderly." Johanna M. Seddon, M.D.,
Sc.M. Director, Epidemiology Unit for Macular Degeneration Research Massachusetts
Eye and Ear Infirmary Harvard Medical School Harvard School of Public Health
"There is growing awareness among both physicians and their patients that nutrition
can play an important role in the prevention of visual loss from age-related
macular degeneration (AMD), the leading cause of irreversible blindness in the
developed world. Two dietary micronutrients, zeaxanthin and lutein, are
carotenoids derived from fruits and vegetables that are uniquely concentrated
in the macula of the human eye where they are likely to protect against blue
light and oxidative damage. While there is compelling epidemiological
data that high levels of these two carotenoids in the diet, blood, and eye may
protect against AMD, mechanistic evidence for their protective effect in living
animals is notably lacking.
"In the recently published papers by Thomson et al., the authors begin to fill
this void by demonstrating that zeaxanthin supplementation to Japanese quails
affords partial protection against acute light damage to the retina. This
important research work provides further support for the clinical recommendation
that individuals at risk for visual loss from AMD should consider increasing
their intakes of zeaxanthin and lutein through their diet or through nutritional
supplementation." Paul S. Bernstein, MD, PhD Associate Professor of Ophthalmology
and Visual Sciences Moran Eye Center, University of Utah
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Contact Information for Expert Sources
Principle Investigator:
C. Kathleen Dorey, Ph.D. 781-646-8525 kdorey@earthlink.net
Ophthalmologists:
Johanna Seddon, M.D. Departments of Ophthalmology and Epidemiology Mass
Eye and Ear Infirmary 617-573-4010 johannna_seddon@meei.harvard.edu Background:
Dr. Seddon was the first to report that higher levels of zeaxanthin /lutein
in the diet or in the plasma were associated with reduced the risk for advanced
stages of AMD. Professor of both ophthalmology and epidemiology, Dr. Seddon
is considered an expert in the dietary influence on the progression of AMD.
She has strong interest in the inherited, familial factors causing AMD.
She showed that AMD was more likely to occur in both members of identical twins
than in both members of fraternal twins, strong evidence for a genetic component
in the pathogenesis of AMD.
Paul S. Bernstein, M.D., Ph.D. Associate Professor of Ophthalmology and Visual
Sciences University of Utah, Moran Eye Center 801-581-6078 paul.bernstein@hsc.utah.edu
Background: Dr. Bernstein is an ophthalmologist who has devoted his career to
the discovery of factors that contribute to AMD and other retinal degenerati
ons. He has investigated whether abnormalities in genes causing recessive inherited
macular degenerations contribute to AMD, and has contributed to the advancement
of understanding of macular pigments. Dr. Bernstein has conducted research
on proteins that mediate the uptake of carotenoids in the human macula, and
recently developed new methods that permit measurement of macular pigment
in patients with AMD. A statement from Dr. Bernstein is enclosed.
Macular Pigment Experts:
John T. Landrum, Ph.D. Chemistry Department Florida International University
305-348-3091 landrumj@fiu.edu Background: Dr. Landrum conducted groundbreaking
research that demonstrated donor eyes with AMD have lower concentrations lutein
and zeaxanthin, the components of macular pigment. Dr. Landrum and his
colleague, Dr. Bone, also demonstrated that human subjects taking lutein or
zeaxanthin have increased macular pigment. (Alert: since the same
two subjects took lutein for several months before they took the zeaxanthin,
their conclusion that lutein raised macular pigment more is a controversial
interpretation.)
Billy Hammond, Ph.D. University of Georgia's Department of Psychology 706-542-4812
bhammond@egon.psy.uga.edu Background: Dr. Hammond is noted for his work showing
that dietary supplementat ion results in elevated macular pigment, and for work
showing that macular pigment is lower in subjects who are smokers, female, older,
obese, or have blue or green eyes. Numerous studies have shown that advanced
age and smoking dramatically increase risk for AMD. The other factors
have been associated with risk for AMD in some studies, but not in others.
Experts in Carotenoid Protection:
Norman Krinsky, Ph.D Emeritus Department of Biochemistry, School of Medicine
U.S. Department of Agriculture Human Nutrition Research Center on Aging Tufts
University School of Medicine 617-636-6861 norman.krinsky@tufts.edu Background:
Dr. Krinsky has authored numerous articles, including a recent review article
on biological mechanisms for the protective action of xanthophyl ls (e.g. zeaxanthin)
(J. Nutrition, 2002, 132:540-542). He is perhaps best known for his work
on the anti-oxidant characteristics of carotenoids, but he has numerous articles
on the metabolism of carotenoids to retinoids and retinoic acids, (both molecules
that play an important role in development and normal tissue function).
His recent work has focused on the role of cleavage products of b-carotene in
inhibiting growth of breast cancer cells.
Alice Adler, Ph.D. Carotenoid Biochemist: Macular Pigment & Carotenoid Binding
Proteins Schepens Eye Research 617-912-7428 aadler@vision.eri.harvard.edu Background:
Dr. Adler is a biochemist who has worked on the transport of carotenoids in
the eye, and their role in the eye. She was the first scientist to identify
a protein that could bind Vitamin A and transport it across the space between
the photoreceptors that need it to make rhodopsin (the visual pigment) and the
retinal pigment epithelial cells that store retinol and convert it to a form
that the photoreceptors can use. More recently, Dr. Adler identified xanthophyll-binding
proteins in the human retina, and proposed that they bind to the same site on
microtubules that binds taxol, a compound used to treat breast cancer.
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